With an FDA review underway, Johnson & Johnson is aiming to “fundamentally change” how bladder cancer is treated.

That’s how Biljana Naumovic, president of J&J’s U.S. solid tumor business, described the positioning of the company’s TAR-200, which is in the process of an FDA rolling submission as a treatment for Bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS).

J&J’s ambition will likely bring TAR-200—an intravesical system designed to locally deliver the chemotherapy gemcitabine into the bladder—into competition with ImmunityBio’s immunotherapy Anktiva. And, as the threat of competition looms, ImmunityBio isn’t playing sitting duck. 

“There’s nobody [who] has a median of [complete response] of over 45 months” like Anktiva does, Patrick Soon-Shiong, M.D., executive chairman and chief scientific and medical officer of ImmunityBio, said in an interview with Fierce Pharma.

Before their expected market showdown, the battle between TAR-200 and Anktiva is playing out in data drops at the American Urological Association’s (AUA's) 2025 annual meeting in Las Vegas.
 

J&J’s offense
 

At AUA, J&J provided updated data from cohort 2 of the phase 2b Sunrise-1 trial. As of March 2025, TAR-200 achieved a complete response (CR) in 82.4% of 85 patients with BCG-unresponsive high-risk NMIBC CIS with or without papillary disease.

Among the responders, 52.9% were still in remission at one year, when 86.6% were spared from bladder removal. Among the 11 patients who completed two years of treatment, nine remained in response. The median duration of response was 25.8 months.

TAR-200’s CR rate is the highest recorded among currently available therapies, Mark Wildgust, Ph.D., vice president of oncology global medical affairs for J&J Innovative Medicine, noted in an interview with Fierce Pharma.

Anktiva, used in combination with BCG, was approved last year based on a 62% CR. Merck & Co.’s Keytruda got its 2020 FDA nod in the same setting with a 41% CR, and Ferring Pharmaceuticals’ gene therapy Adstiladrin followed in 2022 with a 51% rate.

In addition, at the AUA meeting, CG Oncology reported a 75.5% CR for its oncolytic virus candidate cretostimogene grenadenorepvec from the phase 3 Bond-003 Cohort C study in a similar bladder cancer population.

In December, Protara Therapeutics unveiled an early 80% CR for its investigational cell therapy TARA-002, albeit from just five BCG-unresponsive patients. The number rose to 100% CR among the five patients, according to an update at AUA. 

A high CR and so-far durable responses aren’t the only things that J&J’s Wildgust and Naumovic argued could potentially make TAR-200 the new treatment of choice in the field. The drug-device combo also offers urologists and patients a high degree of convenience, the two execs said.

Other therapies are instilled into the bladder and may require patients to stay hours in the urology practice and, for one therapy, remain for about three hours of monitoring by a nurse every treatment session, Naumovic noted. That can be very cumbersome for those practices, she said.

Keytruda has further struggled to take off in NMIBC because urologists are not comfortable with dealing with some immune-related side effects, she added.

By comparison, TAR-200 is an off-the-shelf device that’s put in the patient’s bladder via cystoscopy, a common in-office procedure among urologists that Naumovic said is “in their DNA.” The procedure takes between one and two minutes and does not require special biosafety handling in a separate room.

The device is replaced after three weeks, at which time the physician can simultaneously examine the bladder to assess whether the treatment is working.

“This is what they really like,” Naumovic said. “It’s a really convenient thing for a physician and for a patient, very reassuring.”

After running this cycle for six months, the treatment interval is extended to once every three months through Week 96.

Given TAR-200’s data and product profile, J&J is very bullish about the drug’s market potential.

“In all the research that we have done, I have absolutely no reason to believe that they will use anything else but us once they fail BCG,” Naumovic said. She acknowledged, however, that TAR-200 won’t reach that level of penetration immediately.
 

ImmunityBio’s defense
 

Losing to TAR-200 in the CR rate comparison, ImmunityBio is instead focused on duration of response.

In an update from the Quilt-3.032 trial provided at AUA, among 77 patients who belong to Anktiva’s current FDA label, 51% of complete responders to the Anktiva-BCG regimen were still tumor-free at 45 months. The median duration of complete response stood at 45.4 months, a level that Soon-Shiong said is unprecedented.

What's more, among responders in a broader group of 100 patients with BCG-unresponsive NMIBC CIS, 84% didn’t have to have their bladder removed after three years.

Soon-Shiong has a biological theory to explain Anktiva’s durability showing, and he questions whether J&J’s TAR-200 can match it.

“I’m now educating the field of urologists about a thing called neutrophil-lymphocyte ratio,” Soon-Shiong said.

He pointed to a 2018 BMC Urology study by researchers at Technion – Israel Institute of Technology indicating that a high neutrophil-lymphocyte ratio was a significant predictor of disease recurrence in NMIBC, especially in those BCG-experienced patients.

Soon-Shiong acknowledged that chemotherapy can induce a quick response. But chemo would wipe out the lymphocytes while upregulating immune-suppressive Treg cells, he said.

By contrast, Anktiva, as an IL-15 receptor agonist, leads to proliferation and activation of lymphocytes such as NK, CD8+ and memory T cells without upregulating Treg cells, according to Anktiva’s FDA label.

The ImmunityBio chief also pointed to Anktiva’s tolerability profile. Combining two cohorts of 180 total patients with either NMIBC CIS or NMIBC papillary disease in Quilt-3.032, treatment-related adverse events of grade 3 occurred in six (3%) patients, with no grade 4 or 5 events. 

In two cohorts of patients in Sunrise-1 with either CIS or papillary tumors, about 13% had a grade 3 or above treatment-related adverse event while on TAR-200, and about 6% had at least one serious event. While J&J observed stable quality of life among patients in its NMIBC CIS cohort, Soon-Shiong argued that the pain associated with chemo treatment can be a burdensome problem for some patients.

Despite Anktiva’s novel mechanism, the drug struggled to gain traction last year, with only $7.2 million sales in the last three months of 2024. 

That was before Anktiva was issued a permanent J-code, which facilitates smoother reimbursement, in January, Soon-Shiong noted. ImmunityBio recently shared its estimated first-quarter sales of $16.5 million.

Further, through a collaboration with the Serum Institute of India, ImmunityBio is solving a BCG shortage problem, which is key for Anktiva uptake because the drug is used together with BCG. The partners are now offering a recombinant BCG under an FDA-authorized expanded access program.
 

Going beyond BCG-unresponsive NMIBC CIS
 

Both J&J and ImmunityBio are looking to expand their drugs’ indications, potentially first to the larger BCG-unresponsive NMIBC papillary disease population. About 90% of NMIBC cases are papillary.

A few days ago, ImmunityBio announced that it had submitted an FDA application for Anktiva plus BCG in that papillary disease population based on data from the Quilt-3.032 trial.

That marked a U-turn from the company’s messaging last year. Because the papillary cohort of Quilt-3.032 evaluated disease-free survival, a time-to-event endpoint, the FDA had told ImmunityBio that a randomized trial would be required to pursue an approval in this subtype. At that time, Soon-Shiong said the biotech was still trying to finalize a registrational trial plan with the agency.

“What happened is the duration of response,” Soon-Shiong explained. “No matter how many randomized trials that we would do […] there’s no docetaxel that’s going to give you cystectomy-free for over 80% in three years.”

In cohort B of Quilt-3.032 among 80 patients with papillary disease, 81.8% of patients avoided bladder removal after three years, according to a July 2024 data cutoff. That bladder-sparing percentage is the highest recorded to date in this population, according to ImmunityBio.

J&J, however, is taking a more cautious pathway.

In cohort 4 of the Sunrise-1 study conducted among 52 papillary disease-only patients, TAR-200 delivered an 81.1% disease-free survival rate at nine months after a median follow-up of 12.8 months, according to results released at AUA. The rates were similar across both high-grade Ta and T1 diseases, which J&J’s Wildgust said are reflective of TAR-200’s sustained tissue penetration.

An approval in BCG-unresponsive CIS patients based on single-arm data is possible because those patients represent a small group that are at high risk of progressing to metastatic disease, Wildgust explained. After long conversations with the FDA, J&J has decided to use a randomized phase 3 trial coded Sunrise-5 testing TAR-200 against chemotherapy to pursue a regulatory approval in the papillary population.

Also eyeing an indication in BCG-naïve NMIBC patients, J&J is running the phase 3 Sunrise-3 trial, a 1,000 subject-plus study that has completed enrollment. The trial has three arms comparing either TAR-200 alone or TAR-200 plus J&J’s PD-1 inhibitor cetrelimab against BCG.

The phase 2b Sunrise-1 study had a cohort of TAR-200 in combination with cetrelimab in BCG-unresponsive patients. But J&J didn’t pursue that approach because the tumor response was similar to TAR-200 monotherapy with added toxicity, Wildgust explained.

However, the company still wants to test the combo in the BCG-naïve setting in the hope that it may add longer duration to the responses or show better benefit-risk profile in certain subsets of patients.

For its part, ImmunityBio has a long-running phase 2b Quilt-2.005 trial for Anktiva plus BCG in BCG-naïve patients.